L01XX41 - Eribulin |
Propably not porphyrinogenic |
PNP |
Important Information
Risk for gastrointestinal adverse events in the form of nausea, vomiting, diarrhoea and constipation motivates vigilance against insufficient intake of food, especially of carbohydrate.
Side effects
Common adverse reactions of eribulin that can be confused with an acute porphyric attack are nausea, vomiting diarrhoea and constipation. These side effects may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake.
Rationale
Eribulin is not an inducer or mechanism-based inhibitor of any major CYP enzymes, and therefore no pharmacokinetic porphyrinogenic effects are suspected.
Chemical description
Eribulin is a furopyran, a structurally simplified synthetic analogue of halichondrin B which is a natural product isolated from the marine sponge Halichondria okadai.
Therapeutic characteristics
Eribulin is an antineoplastic agent indicated for the treatment of adult patients with locally advanced or metastatic breast cancer and for adult patients with unresectable liposarcoma.
It is administered intravenously.
Metabolism and pharmacokinetics
Eribulin is a substrate of CYP 3A4, but up to 70 per cent of the administered dose is eliminated unchanged through biliary excretion. Eribulin does not inhibit the CYP enzymes CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 or 2E1 at relevant clinical concentrations, but is described as a mild inhibitor of CYP 3A4 (SPC).
In an in vitro study eribulin did not induce CYP3A expression or activity but showed some potential for inhibition of CYP3A4-mediated metabolism as a substrate competitor. This reversible inhibition was determined to be not clinically relevant, based on the enzyme-kinetic characterization and the lack of NADPH- and time-dependent enzyme inhibition (Zhang 2008).
No in vivo drug-drug interaction studies have been carried out.
References
- Scientific articles
- Zhang ZY, King BM et al. Delineation of the interactions between the chemotherapeutic agent eribulin mesylate (E7389) and human CYP3A4. Cancer Chemother Pharmacol. 2008 Sep;62(4):707-16 PMID 18431572. #3236
- Summary of Product Characteristics
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Halaven. (Last edition: August.2017). #3235
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